The aim of the proposed research is the development of new methodology to aid classical cytology and pathology in the detection and diagnosis of disease. In classical cytology, visual inspection is used to detect changes in the morphology of cells obtained from body fluids, or by exfoliation or thin needle biopsy, while in classical pathology stained tissue sections are examined visually. The novel methods being developed in the PI's laboratory, referred to as spectral cytology and spectral pathology, are based on optical measurements, which detect variations in biochemical composition of cells quantitatively, and which use objective algorithms to quantify the spectral results in terms of disease. These diagnostic algorithms are trained using the correlation between spectral data and classical cytology/pathology as the gold standard. The efforts carried out in the Pi's laboratory, and results from other groups worldwide, have demonstrated that spectral cytology is an extraordinarily sensitive method for detecting variations in cellular properties. For example, spectral cytology at the single cell level can be used to distinguish normal from cancerous epithelial cells, normal lymphocytes from lymphoma cells, and even closely related normal cells from each other (e.g. B- and T-lymphocytes, activated and non-activated lymphocytes). Relevance: The methods of optical diagnoses being developed in the PI's laboratory will augment presently available methods of cytology and pathology to screen exfoliated cells for disease, and diagnose tissue sections from biopsies for the same diseases. The optical methods are entirely machine-based and computer-interpreted and thus, reduce the workload in diagnostic laboratories, increase the overall accuracy and decrease the time required to render medical diagnoses.